Off-the-shelf CD123 CAR-NK for R/R AML

Официальное название

Safety and Efficacy of Universal Off-the-shelf CAR-NK Cells Targeted CD123 (JD123 Injection) in the Treatment of Refractory or Relapsed CD123-positive Acute Myeloid Leukemia

Обзор

This is a single-centre, single-arm, open-label, first-in-human (FIH) study to evaluate the safety, tolerability and preliminary efficacy of universal Off-the-shelf CAR-NK cells targeted CD123 (JD123 injection) in the treatment of refractory or relapsed CD123-positive acute myeloid leukemia (AML).

Подробное описание

This is a dose-escalation study of CD123-targeted chimeric antigen receptor modified natural killer cells (CAR-NK) derived from a healthy donor. The relapsed/refractory AML patients will receive FC (F, Fludarabine, C, Cyclophosphamide) chemotherapy followed by infusion of JD123 injections. No graft-versus-host disease (GVHD) prevention will be conducted before or after infusion. Dose-limiting toxicity, incidence of adverse events, disease response and PK/PD will be detected post-infusion.

Вмешательства

• Препарат JD123 injection
  JD123 injection is an universal Off-the-shelf CD123-targeted chimeric antigen receptor modified natural killer cells (CAR-NK) therapy derived from a healthy donor.

Первичные конечные точки

• 1-month DLTs [Срок оценки: 1-month]

Вторичные конечные точки (6)

• 3-month CR/CRi [Срок оценки: 3-month]
• 1-year PFS [Срок оценки: 1-year]
• 1-year OS [Срок оценки: 1-year]
• 1-year MRD(-) [Срок оценки: 1-year]
• 3-month AUC [Срок оценки: 3-month]
• 3-month Peak [Срок оценки: 3-month]

Критерии участия

Критерии включения

• Age ≥ 18 years old, no gender or race;
• Expected survival period ≥ 3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2;
• The diagnosis of AML with bone marrow biopsy, immunohistochemistry or Flow cytometry definitively positive for CD123 and met the following criteria:

A. Diagnostic criteria for relapsed AML: after complete remission (CR), leukemia cells reappeared in peripheral blood or blast cells in bone marrow ≥ 5% (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration; B. Diagnostic criteria for refractory AML: naive patients who were ineffective after 2 courses of standard regimens; patients relapsed within 12 months who underwent consolidation and intensive therapy after CR; patients relapsed after 12 months but were ineffective after conventional chemotherapy; Patients with two or more relapses; patients with persistent extramedullary leukemia; Patients relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) C. Minimal Residual Disease (MRD) positive only or relapse: Patient is minimal residual disease (MRD) positive, as assessed on bone marrow aspirate (BMA) by Multiparameter Flow Cytometry (MFC) at time of Treatment Eligibility assessment.

• Adequate organ function:

A. Liver function: ALT≤3×ULN, AST≤3×ULN, total bilirubin≤2×ULN; B. Coagulation function: international normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤ 1.5×ULN; C. Renal function: serum creatinine≤1.5×ULN or creatinine clearance rate ≥30mL/min; D. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%; 6. Women of child-bearing potential and all male participants must use effective methods of contraception for at least 12 months after infusion.; 7. Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.

Критерии исключения

• Active Central nervous system leukemia;
• Known contraindication to the protocol defined lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide;
• Systemic use of hormones within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids);
• Any active infection requiring systemic therapy by intravenous infusion within 14 days prior to the first dose of study drug, including: HBV, HCV, HIV, syphilis infection, or active pulmonary tuberculosis.
• History of hypersensitivity reactions to murine protein-containing products, or macromolecular biopharmaceuticals such as antibodies or cytokines;
• Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment;
• Women who are pregnant (urine/blood pregnancy test positive) or lactating;
• Suffering from a serious autoimmune disease or immunodeficiency disease; 9 Suffering from mental illness;

10\. Known alcohol dependence or drug dependence; 11. According to the investigator's judgment, the patient has other unsuitable grouping conditions.

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Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking University People's Hospital — Пекин

Идентификаторы

NCT: NCT06201247 · 2023PHD016-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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